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Epigenetic regulation of immune cells in systemic lupus erythematosus: insight from chromatin accessibility. 系统性红斑狼疮免疫细胞的表观遗传调控：从染色质可及性中窥见一斑。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-02 DOI: 10.1080/14728222.2024.2375372
Zhao-Xing Gao, Tian He, Peng Zhang, Xiao Hu, Man Ge, Yi-Qing Xu, Peng Wang, Hai-Feng Pan
{"title":"Epigenetic regulation of immune cells in systemic lupus erythematosus: insight from chromatin accessibility.","authors":"Zhao-Xing Gao, Tian He, Peng Zhang, Xiao Hu, Man Ge, Yi-Qing Xu, Peng Wang, Hai-Feng Pan","doi":"10.1080/14728222.2024.2375372","DOIUrl":"10.1080/14728222.2024.2375372","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic Lupus Erythematosus (SLE) is a multi-dimensional autoimmune disease involving numerous tissues throughout the body. The chromatin accessibility landscapes in immune cells play a pivotal role in governing their activation, function, and differentiation. Aberrant modulation of chromatin accessibility in immune cells is intimately associated with the onset and progression of SLE.</p><p><strong>Areas covered: </strong>In this review, we described the chromatin accessibility landscapes in immune cells, summarized the recent evidence of chromatin accessibility related to the pathogenesis of SLE, and discussed the potential of chromatin accessibility as a valuable option to identify novel therapeutic targets for this disease.</p><p><strong>Expert opinion: </strong>Dynamic changes in chromatin accessibility are intimately related to the pathogenesis of SLE and have emerged as a new direction for exploring its epigenetic mechanisms. The differently accessible chromatin regions in immune cells often contain binding sites for transcription factors (TFs) and cis-regulatory elements such as enhancers and promoters, which may be potential therapeutic targets for SLE. Larger scale cohort studies and integrating epigenomic, transcriptomic, and metabolomic data can provide deeper insights into SLE chromatin biology in the future.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury. PDE4B抑制剂在脂肪组织功能障碍和慢性肝损伤中的治疗前景。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-06-19 DOI: 10.1080/14728222.2024.2369590
Dalton W Staller, Robert G Bennett, Ram I Mahato
{"title":"Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury.","authors":"Dalton W Staller, Robert G Bennett, Ram I Mahato","doi":"10.1080/14728222.2024.2369590","DOIUrl":"10.1080/14728222.2024.2369590","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic liver disease (CLD) is a complex disease associated with profound dysfunction. Despite an incredible burden, the first and only pharmacotherapy for metabolic-associated steatohepatitis was only approved in March of this year, indicating a gap in the translation of preclinical studies. There is a body of preclinical work on the application of phosphodiesterase 4 inhibitors in CLD, none of these molecules have been successfully translated into clinical use.</p><p><strong>Areas covered: </strong>To design therapies to combat CLD, it is essential to consider the dysregulation of other tissues that contribute to its development and progression. As such, proper therapies must combat this throughout the body rather than focusing only on the liver. To detail this, literature characterizing the pathogenesis of CLD was pulled from PubMed, with a particular focus placed on the role of PDE4 in inflammation and metabolism. Then, the focus is shifted to detailing the available information on existing PDE4 inhibitors.</p><p><strong>Expert opinion: </strong>This review gives a brief overview of some of the pathologies of organ systems that are distinct from the liver but contribute to disease progression. The demonstrated efficacy of PDE4 inhibitors in other human inflammatory diseases should earn them further examination for the treatment of CLD.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of adipokines in the pathogenesis of psoriasis - a focus on resistin, omentin-1 and vaspin. 脂肪因子在银屑病发病机制中的作用--重点关注抵抗素、网织蛋白-1 和 vaspin。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-05 DOI: 10.1080/14728222.2024.2375373
Kajetan Kiełbowski, Estera Bakinowska, Aleksandra Wiktoria Bratborska, Andrzej Pawlik
{"title":"The role of adipokines in the pathogenesis of psoriasis - a focus on resistin, omentin-1 and vaspin.","authors":"Kajetan Kiełbowski, Estera Bakinowska, Aleksandra Wiktoria Bratborska, Andrzej Pawlik","doi":"10.1080/14728222.2024.2375373","DOIUrl":"10.1080/14728222.2024.2375373","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic immune-mediated skin condition with several types of manifestation, including psoriatic arthritis. In recent years, studies have demonstrated multiple molecules and mechanisms that play important roles in the pathophysiology of psoriasis. Studies have been conducted to determine the role of adipokines, bioactive peptides secreted by the adipose tissue, in the pathogenesis of inflammatory diseases. These studies have shown that adipokines are dysregulated in psoriasis and their abnormal expression profile could contribute to the inflammatory mechanisms observed in psoriasis.</p><p><strong>Areas covered: </strong>In this review, we discuss the immunomodulatory features of resistin, omentin-1, and vaspin, and discuss their potential involvement in the pathogenesis of psoriasis.</p><p><strong>Expert opinion: </strong>The adipokines resistin, omentin, and vaspin appear to be promising therapeutic targets in psoriasis. It is important to seek to block the action of resistin, either by blocking its receptors or by blocking its systemic effects with antibodies. In the case of omentin and vaspin, substances that are receptor mimetics of these adipokines should be sought and studies conducted of their analogues for the treatment of psoriasis. To introduce these therapies into clinical practice, multicentre clinical trials are required to confirm their efficacy and safety after initial studies in animal models.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Potential of αvβ6 and αvβ1 integrin inhibition for treatment of idiopathic pulmonary fibrosis. αvβ6和αvβ1整合素抑制治疗特发性肺纤维化的潜力。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-02 DOI: 10.1080/14728222.2024.2375375
Serena Bellani, Philip L Molyneaux, Toby M Maher, Paolo Spagnolo
{"title":"Potential of αvβ6 and αvβ1 integrin inhibition for treatment of idiopathic pulmonary fibrosis.","authors":"Serena Bellani, Philip L Molyneaux, Toby M Maher, Paolo Spagnolo","doi":"10.1080/14728222.2024.2375375","DOIUrl":"10.1080/14728222.2024.2375375","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease of unknown cause with a dismal prognosis. Nintedanib and Pirfenidone are approved worldwide for the treatment of IPF, but they only slow the rate of functional decline and disease progression. Therefore, there is an urgent need for more efficacious and better tolerated drugs.</p><p><strong>Areas covered: </strong>αvβ6 and αvβ1 are two integrins overexpressed in fibrotic tissue, which play a critical role in the development of lung fibrosis. They act by converting transforming growth factor (TGF)-β, one of the most important profibrotic cytokine, in its active form. Here, we summarize and critically discuss the potential of a dual αvβ6/αvβ1 integrin inhibitor for the treatment of IPF.</p><p><strong>Expert opinion: </strong>Bexotegrast, a dual αvβ6/αvβ1 integrin inhibitor, has the potential to slow or even halt disease progression in IPF. Indeed, the strong pre-clinical rationale and promising early phase clinical trial data have raised expectations.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathways and targeting avenues of BRAF in non-small cell lung cancer. 非小细胞肺癌中 BRAF 的作用途径和靶向途径。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-04 DOI: 10.1080/14728222.2024.2374742
Evgeny N Imyanitov, Natalia V Mitiushkina, Ekatherina Sh Kuligina, Vladislav I Tiurin, Aigul R Venina
{"title":"Pathways and targeting avenues of BRAF in non-small cell lung cancer.","authors":"Evgeny N Imyanitov, Natalia V Mitiushkina, Ekatherina Sh Kuligina, Vladislav I Tiurin, Aigul R Venina","doi":"10.1080/14728222.2024.2374742","DOIUrl":"10.1080/14728222.2024.2374742","url":null,"abstract":"<p><strong>Introduction: </strong>BRAF is a serine-threonine kinase implicated in the regulation of MAPK signaling cascade. BRAF mutation-driven activation occurs in approximately 2-4% of treatment-naive non-small cell carcinomas (NSCLCs). BRAF upregulation is also often observed in tumors with acquired resistance to receptor tyrosine kinase inhibitors (TKIs).</p><p><strong>Areas covered: </strong>This review describes the spectrum of <i>BRAF</i> mutations and their functional roles, discusses treatment options available for <i>BRAF</i> p.V600 and non-V600 mutated NSCLCs, and identifies some gaps in the current knowledge.</p><p><strong>Expert opinion: </strong>Administration of combined BRAF/MEK inhibitors usually produces significant, although often a short-term, benefit to NSCLC patients with <i>BRAF</i> V600 (class 1) mutations. There are no established treatments for <i>BRAF</i> class 2 (L597, K601, G464, G469A/V/R/S, fusions, etc.) and class 3 (D594, G596, G466, etc.) mutants, which account for up to two-thirds of <i>BRAF</i>-driven NSCLCs. Many important issues related to the use of immune therapy for the management of <i>BRAF</i>-mutated NSCLC deserve further investigation. The rare occurrence of <i>BRAF</i> mutations in NSCLC is compensated by high overall incidence of lung cancer disease; therefore, clinical studies on <i>BRAF</i>-associated NSCLC are feasible.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The pleiotropic CLEC10A: implications for harnessing this receptor in the tumor microenvironment. 多效应 CLEC10A：在肿瘤微环境中利用这种受体的意义。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-07-01 Epub Date: 2024-07-03 DOI: 10.1080/14728222.2024.2374743
Nadia L van der Meijs, Maria Alejandra Travecedo, Filipa Marcelo, Sandra J van Vliet
{"title":"The pleiotropic CLEC10A: implications for harnessing this receptor in the tumor microenvironment.","authors":"Nadia L van der Meijs, Maria Alejandra Travecedo, Filipa Marcelo, Sandra J van Vliet","doi":"10.1080/14728222.2024.2374743","DOIUrl":"10.1080/14728222.2024.2374743","url":null,"abstract":"<p><strong>Introduction: </strong>CLEC10A is a C-type lectin receptor that specifically marks the conventional dendritic cell subsets two and three (cDC2 and DC3). It has a unique recognition profile of glycan antigens, with terminal N-Acetylgalactosamine residues that are frequently present in the tumor microenvironment. Even though CLEC10A expression allows for precise targeting of cDC2 and DC3 for the treatment of cancer, CLEC10A signaling has also been associated with anti-inflammatory responses that would promote tumor growth.</p><p><strong>Areas covered: </strong>Here, we review the potential benefits and drawbacks of CLEC10A engagement in the tumor microenvironment. We discuss the CLEC10A-mediated effects in different cell types and incorporate the pleiotropic effects of IL-10, the main anti-inflammatory response upon CLEC10A binding.</p><p><strong>Expert opinion: </strong>To translate this to a successful CLEC10A-mediated immunotherapy with limited tumor-promoting capacities, finding the right ligand presentation and adjuvant combination will be key.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondria makeover: unlocking the path to healthy longevity. 线粒体改造：开启健康长寿之路。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-06-01 Epub Date: 2023-11-02 DOI: 10.1080/14728222.2023.2277240
Andrés Caicedo, Keshav K Singh
{"title":"Mitochondria makeover: unlocking the path to healthy longevity.","authors":"Andrés Caicedo, Keshav K Singh","doi":"10.1080/14728222.2023.2277240","DOIUrl":"10.1080/14728222.2023.2277240","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Can we suppress chronic systemic inflammation and postpone age-related diseases by targeting the IgG glycome? 我们能通过靶向IgG糖组来抑制慢性全身炎症并延缓与年龄相关的疾病吗？
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-06-01 Epub Date: 2023-11-02 DOI: 10.1080/14728222.2023.2277218
GordAn Lauc
{"title":"Can we suppress chronic systemic inflammation and postpone age-related diseases by targeting the IgG glycome?","authors":"GordAn Lauc","doi":"10.1080/14728222.2023.2277218","DOIUrl":"10.1080/14728222.2023.2277218","url":null,"abstract":"<p><strong>Introduction: </strong>Glycans attached to immunoglobulin G are an important regulator of chronic systemic inflammation, one of the key drivers of aging. As people age, glycans that suppress inflammation are being replaced with inflammation-promoting glycans, but the rate of this conversion is highly individual and is affected by genetic, epigenetic, and environmental factors.</p><p><strong>Areas covered: </strong>This review summarizes key studies of IgG glycosylation changes in aging and disease, effects of lifestyle and pharmacological interventions, and mechanisms that regulate IgG glycosylation.</p><p><strong>Expert opinion: </strong>IgG glycome is an important contributor to the process of aging that can be modulated by both lifestyle and pharmacological interventions. Small molecule drugs that would suppress chronic systemic inflammation by modulation of the IgG glycome are still not available, but since gene network regulating IgG glycosylation has been identified and a high-throughput <i>in vitro</i> screening system is available, it is likely that this highly innovative approach to manage chronic systemic inflammation will be developed soon.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61561694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glycoproteins and longevity: an interview with Professor Gordan Lauc. 糖蛋白与长寿：戈尔丹-劳克教授访谈录。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-06-01 Epub Date: 2024-07-05 DOI: 10.1080/14728222.2024.2375809
Ryan Gilroy, Gordan Lauc
{"title":"Glycoproteins and longevity: an interview with Professor Gordan Lauc.","authors":"Ryan Gilroy, Gordan Lauc","doi":"10.1080/14728222.2024.2375809","DOIUrl":"10.1080/14728222.2024.2375809","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Curing age-related disease, transforming global medicine. 治愈与年龄相关的疾病，改变全球医学。
IF 4.6 2区 医学
Expert Opinion on Therapeutic Targets Pub Date : 2024-06-01 Epub Date: 2023-11-06 DOI: 10.1080/14728222.2023.2277223
Michael Fossel
{"title":"Curing age-related disease, transforming global medicine.","authors":"Michael Fossel","doi":"10.1080/14728222.2023.2277223","DOIUrl":"10.1080/14728222.2023.2277223","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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